GO_REF:0000015

Use of the ND evidence code for Gene Ontology (GO) terms

GO_REF:0000033

Annotation inferences using phylogenetic trees

The current conjugation IBA is placed on the Ral2/Mds3-related node PTN005166285 and is grounded by Ral2's own experimental annotation; PAINT records losses before that node for the ancestral peroxiredoxin functions.

PMID:16823372

ORFeome cloning and global analysis of protein localization in the fission yeast Schizosaccharomyces pombe.

The study used proteome-wide YFP tagging; the Ral2-specific ER call cannot be independently checked from the accessible abstract.

"we determined the localization of 4,431 proteins, corresponding to approximately 90% of the fission yeast proteome, by tagging each ORF with the yellow fluorescent protein."

PMID:2586528

Characterization of the Schizosaccharomyces pombe ral2 gene implicated in activation of the ras1 gene product.

Ral2 encodes a 611 AA protein essential for mating and cell morphology, functioning upstream of Ras1.

"Mutations in the Schizosaccharomyces pombe ral2 gene cause a phenotype indistinguishable from that of the ras1-defective mutant."
Ral2 gene product is involved in activation of the Ras1 protein.

"These results suggest that the ral2 and ras1 gene products interact intimately and that the ral2 gene product is involved in activation of the ras1 protein in S. pombe."

PMID:3071741

Isolation and characterization of Schizosaccharomyces pombe mutants phenotypically similar to ras1-.

Ral2 was identified in a screen for mutants phenocopying ras1 deletion, and epistasis analysis places ral1, ral2, ras1 in a common pathway.

"These results suggest that the ral1, ral2 and ras1 genes may function in a common pathway in that order."

PMID:18257517

Phosphoproteome analysis of fission yeast.

Ral2 is phosphorylated at Ser-604.

"2887 distinct phosphorylation sites were identified from 1194 proteins with an estimated false-discovery rate of <0.5% at the peptide level."

PMID:2038319

Identification of a GTPase-activating protein homolog in Schizosaccharomyces pombe.

The Ras-GTPase cycle in S. pombe involves the ral2 gene product as a positive regulator of Ras1, proposed to act either as a GDP-GTP exchange factor or as a negative regulator of the Gap1 GTPase- activating protein. Gap1 and Ste6 play antagonistic roles in this cycle.

"we suggest that this Ras-GTPase cycle involves the ra12 gene product, another positive regulator of Ras1 whose homologs have not been identified in other organisms, which could function either as a second GDP-GTP-exchanging protein or as a factor that negatively regulates Gap1 activity."

file:SCHPO/ral2/ral2-deep-research-falcon.md

Falcon (Edison Scientific) deep research report on S. pombe ral2 (P15258 / SPBC21.05c).

Across independent fission-yeast genetics studies, ral2 is most consistently supported as a positive regulator of Ras1 signaling, functioning in Ras1-dependent control of mating competence and cell shape/polarized growth.

"Across independent fission-yeast genetics studies, ral2 is most consistently supported as a **positive regulator of Ras1 signaling** (a “putative activator of Ras1”), functioning in Ras1-dependent control of mating competence and cell shape/polarized growth."
Genetic epistasis places ral2 in the Ras-GTPase cycle: gap1 null bypasses the requirement for ral2 to keep Ras GTP-bound, and activating point mutations in the ras1 ORF suppress ral2 defects, supporting ral2 acting on Ras1 activation rather than on ras1 expression.

"Point mutations in the **ras1 ORF** can suppress ral2 defects, supporting the idea that ral2 acts upstream of or on Ras1 activation rather than simply affecting ras1 expression."
ral2 is mechanistically framed as a positive regulator of Ras1 whose exact biochemistry was unresolved, hypothesized to be either a GDP->GTP exchange-type activator for Ras1 or an indirect negative regulator of the Ras1 GAP Gap1.

"ral2 is treated as a **positive regulator of Ras1** whose mechanism was unresolved: the ral2 product was hypothesized either to function as a **GDP→GTP exchange-type activator** for Ras1 or to act indirectly by **negatively regulating the Ras1 GAP Gap1**, thereby increasing Ras1-GTP."
S. pombe Ral2 is reported to contain three Kelch repeats at its N-terminus and is placed in the Ras1-Scd pathway; Kelch repeats are protein-protein interaction modules, consistent with an adaptor/scaffold role rather than a defined catalytic activity.

"describe *S. pombe* Ral2 as containing **three Kelch repeats at its N-terminus**, and place it in the **Ras1–Scd pathway**."
A 2024 review of sexual differentiation initiation in S. pombe continues to classify ral2 as a Ras1-Scd pathway protein, reflecting ongoing recognition of ral2 as a Ras-pathway component.

"ral2 is included as a “Ras1–Scd pathway protein” in a curated pathway table, reflecting continued recognition of ral2 as a Ras-pathway component in modern syntheses of mating control."
No direct subcellular localization evidence (e.g., microscopy) for S. pombe Ral2 was retrieved; the available primary literature supports genetic/pathway placement and domain-level inference, so the high-throughput ER localization should be treated cautiously.

"No direct subcellular localization evidence for *S. pombe* Ral2 (e.g., microscopy localization) was retrieved in the accessible texts used here; the available sources primarily provide genetic/pathway placement and domain-level inference."